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Biomedical subjects

M D Klein

Publications and source records attributed to M D Klein.

At least 73 records · Page 4Linked to original sources
PubMed1987

Treatment of angina pectoris and hypertension with sustained-release calcium channel-blocking drugs.

Sustained-release diltiazem (D-SR) and sustained-release verapamil (V-SR) when given twice a day have been successfully used to treat both essential hypertension and angina pectoris. Review of available studies indicates that 120 to 180 mg D-SR twice a day and 240 mg V-SR once or twice a day can lower diastolic pressure in 40% to 80% of patients with essential hypertension and that the drugs may be especially useful in patients with low-renin hypertension such as elderly and black populations. D-SR and V-SR prolong treadmill capacity and reduce frequency of angina in patients with stable effort angina. Improvement is mediated primarily by a reduction in resting and submaximal exercise heart rate. Biopharmaceutics of D-SR and V-SR feature a prolonged apparent plasma half-life and reduced peak-to-trough plasma concentration ratios during steady-state dosing.

Angina Pectoris↗
PubMed1986

Regular formulation and sustained-release verapamil therapy in normotension and in mild to moderate hypertension.

Calcium entry blocker drugs have hypotensive effects that are mediated by both cardiac and noncardiac actions. Dihydropyridine calcium blockers, such as nifedipine and nicardipine, are potent vascular smooth muscle relaxants that lower blood pressure by decreasing peripheral arteriolar resistance. Reflex tachycardia, however, may blunt the magnitude of their hypotensive effect, especially in patients with increased baroreflex sensitivity. Nondihydropyridine calcium blocker drugs, such as verapamil and diltiazem, exert their hypotensive action by both cardiac and peripheral circulatory mechanisms. These drugs also act as arteriolar vasodilators. In addition, they slow the heart rate by decreasing the automaticity of sinoatrial pacemaker cells in the heart. The combined negative chronotropic and vasodilatory actions are especially useful in hypertensive patients with baroreflex sensitivity who are prone to fast heart rates, and in hypertensive patients with associated coronary artery disease. Coronary heart disease patients with or without coexisting hypertension usually show reduction in systolic blood pressure (SBP) and heart rate (HR) both at rest and during submaximal exercise on the treadmill or bicycle. A reduced double product (SBP X HR) with submaximal exertion results in a decrease in cardiac work and correlates with enhanced exercise capacity and delay in onset of angina during exercise testing. In some patients with both hypertensive and coronary heart diseases and ventricular dysrhythmias emerging during exercise, verapamil may confer antiarrhythmic as well as antihypertensive and antianginal benefits. At present, calcium blocker drugs, which have an elimination half-life of 3 to 6 hours, must be given 3 times a day for effective antihypertensive control.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1986

Efficacy and safety of sustained-release diltiazem in stable angina pectoris.

The safety and efficacy of a sustained-release preparation of diltiazem (diltiazem-SR), with dose levels of 240 and 360 mg/day, were assessed in 18 patients with stable angina of effort. A double-blind, placebo-controlled, randomized, crossover protocol was used. Diltiazem-SR, when given twice daily, reduced the frequency of weekly anginal attacks from 9.3 +/- 10.4 with placebo to 3.7 +/- 4.7 with 240 mg/day and to 3.1 +/- 4.7 with 360 mg/day (both p less than 0.01 compared with placebo). Treadmill time was increased from 410 +/- 180 seconds during the placebo phase to 519 +/- 177 seconds during the 240-mg/day dose and to 506 +/- 182 seconds during the 360-mg/day dose of diltiazem-SR (both p less than 0.01 compared with placebo). The time to the onset of angina and ischemic ST-segment depression were similarly prolonged by both doses of diltiazem-SR. The beneficial effects of diltiazem-SR appeared partly due to a reduction in the heart rate during submaximal exercise. Diltiazem-SR is effective and safe for the treatment of angina of effort when given twice daily.

Aged↗
PubMed1986

Gastroesophageal reflux in children: is there a place for the upper gastrointestinal study?

Objective tests for gastroesophageal reflux in children have shown only fair correlation with clinical symptoms. Thirty-four children referred to the pediatric surgery service for evaluation of gastroesophageal reflux had both 24-hour pH probe monitoring and standardized upper gastrointestinal examinations. A total of 16 children (47%) had documented significant or pathologic gastroesophageal reflux, 11 on pH monitors and 9 on contrast examinations. There were 4 in whom both tests were positive. None of the pH monitoring criteria correlated with the radiographic studies. The patient population documented by contrast study did not differ from the general test-positive population by age or associated clinical findings. The 2 studies probably measure different aspects of significant gastroesophageal reflux, are confirmatory and complementary, and must be correlated with the clinical symptoms.

Adolescent↗
PubMed1986

Hemorrhagic complications during extracorporeal membrane oxygenation: prevention and treatment.

Hemorrhage related to systemic heparinization is the major complication of extracorporeal membrane oxygenation (ECMO). Intracranial hemorrhage (ICH) is the most devastating complication. ICH developed in 13 of our 25 ECMO patients (52%). Six died, six survived with normal neurologic function, and one is severely impaired. In nine of 13 patients (69%) ECMO was discontinued when serial cranial ultrasounds showed progressive ICH. Seizures developed in six infants while receiving ECMO, and ICH developed in all. There is a correlation between hypertension and ICH. A hypertension index (hours systolic BP greater than 90/hours receiving ECMO) was 0.1 +/- 0.12 for infants without ICH and 0.37 +/- 0.28 for infants with ICH (P less than .05). ICH developed in 79% of the patients with an index greater than 0.1. Twenty neck explorations were required in the first 20 patients for incisional bleeding (mean blood loss, 21.9 +/- 18.0 mL/kg/d). We now use fibrin glue following cannulation and have done only one neck exploration in the last five patients (mean blood loss, 2.8 +/- 2.2 mL/kg/d, P less than .05). Endobronchial bleeding has responded to phenylephrine lavage and increased positive end-expiratory pressure. We have controlled pleural space bleeding with topical thrombin. None of the hemorrhagic complications encountered correlate with the activated clotting time or the amount of heparin used. There is an increased risk of hemorrhage associated with platelet counts less than 100,000/microL for 75% of a day (P less than .05) so that aggressive platelet transfusion remains important in preventing hemorrhagic complications during ECMO.

Cerebral Hemorrhage↗
PubMed1985

Hospital readmissions among survivors six months after myocardial revascularization.

One neglected but important measure of early morbidity after coronary artery bypass graft (CABG) operations is rehospitalization. As part of a prospective study of recovery after elective CABG procedures conducted at four academic medical centers, data from all readmissions occurring within the first six postoperative months were collected for 326 patients. A total of 24% of patients had readmissions. The most common categories of readmission discharge diagnoses were cardiac (57%), noncardiac (26%), and surgical sequelae (17%). Factors from the initial hospitalization identified as risk factors for rehospitalization included: length of stay in intensive care unit after surgery, severe noncardiac complications, duration of preoperative cardiac symptoms, intra-aortic balloon insertion, and preoperative resting angina. These findings help to identify a subset of at risk patients for whom more careful surveillance might be beneficial.

Adult↗
PubMed1985

Long-term survival of dogs maintained solely on intraperitoneal nutrition.

Total intraperitoneal nutrition (IPN) for patients in whom enteral nutrition is impossible would utilize the access techniques of peritoneal dialysis and avoid long-term central venous cannulation. We previously demonstrated that a lipid emulsion was quantitatively absorbed from the dog's peritoneal cavity over four hours. We have now investigated the efficacy of total IPN in dogs over periods up to four weeks. A solution of 1.25% amino acids, 1% glucose, 77 mEq/L Na, 4 mEq/L K, and 81 mEq/L Cl (AGE) was administered IP at 65 mL/kg every 12 hours in combination with 25 mL/kg of 20% lipid emulsion to five dogs allowed free access to food and water for ten days. Sixty percent of administered fluid was absorbed. When AGE and lipid were administered separately every 12 hours to six dogs, 90% was absorbed. In five dogs kept strictly NPO for two weeks while receiving alternating AGE and lipid, absorption averaged 60%. Removing the amino acids allowed absorption to remain at 70% for two weeks, although it dropped to 40% by four weeks. Nine dogs were maintained for a mean of 3.5 weeks while strictly NPO using a solution of 1% glucose and electrolytes at 120 mL/kg every 12 hours with 50 mL/kg of 20% lipid given at a third separate infusion. During the fourth week, they absorbed 118 mL/kg/24 hours of fluid and 26 calories/kg/24 hours. Body weight decreased to 75% of control over four weeks. Complete blood cell count (CBC), Na, K, Cl, total protein (TP), SGOT, and alkaline phosphatase (AP) remained unchanged during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1985

Transpleural repair of esophageal atresia without a primary gastrostomy: 240 patients treated between 1951 and 1983.

Esophageal atresia with distal tracheoesophageal fistula has been treated at one institution between 1951 and 1983 primarily by prompt transpleural repair without gastrostomy. Two hundred and seventy one patients are assigned to three time periods: (1) 1951 to 1963, prior to modern intensive care; (2) 1964 to 1973, the initial era of mechanical ventilation; and 1974 to 1983, the era of readily available ventilators and TPN. During these time periods mean birthweight decreased from 2,780 g to 2,670 g to 2,500 g, while the incidence of associated anomalies increased from 41% to 44% to 55%. Eleven patients had no operation or gastrostomy only and died. Twenty (predominantly in the early years) had staged repairs with initial gastrostomy and fistula ligation. Primary anastomosis was done in 240 patients regardless of birth weight, 229 of which were by the transpleural approach. Gastrostomy was performed primarily in 28 patients for varied indications. Operative mortality (definitive as well as staged repairs) fell over the three time periods from 44% to 15% to 7%. Anastomotic leaks occurred in 20% of patients who underwent primary repair regardless of the time period. The mortality associated with a leak, however, decreased from 88% to 47% to 0%. Anastomotic strictures requiring more than two dilatations occurred in 15% in all periods. The overall incidence of recurrent fistula was 5%. Of 200 patients surviving the initial hospitalization, follow-up longer than 2 months is available for 156 patients with a median follow-up of 30 months. There were 15 late deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1985

Congenital diaphragmatic hernia.

Congenital diaphragmatic hernia continues to be a critical problem in neonatal surgery. Despite the apparent simplicity of the anatomic defect, the physiology is complex, and survival remains uncertain. Surgical success has been achieved, but we recognize that the barrier to survival is pulmonary parenchymal and vascular hypoplasia as well as the complex syndrome of persistent fetal circulation. In many ways the problem of diaphragmatic hernia is as much of an enigma to today's physician-scientist as it was to Bochdalek in the nineteenth century. The treatment of respiratory distress after repair of congenital diaphragmatic hernia has brought out the most creative and innovative efforts of pediatric surgeons in both the laboratory and the intensive care unit.

Animals↗
PubMed1985

Venovenous perfusion in ECMO for newborn respiratory insufficiency. A clinical comparison with venoarterial perfusion.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) has been successful in the treatment of newborns less than 1 week of age and greater than 2000 gm birthweight with respiratory failure resistant to current medical and surgical management. While VA ECMO supports the heart as well as the lungs, it has the disadvantage of requiring carotid artery ligation and the possibility of perfusing air bubbles or particles into the arterial tree. We have treated 11 newborns with respiratory failure with venovenous (VV) ECMO returning the oxygenated blood to a cannula in the distal iliac vein. We compared these patients with 16 patients treated during the same period of time with VA ECMO. Three of the 11 VV patients required conversion to VA ECMO because of inadequate oxygenation and unstable hemodynamic situations. Ten of the 11 VV patients survived. Eleven of the 16 VA patients survived. The better survival in these patients treated with VV ECMO is attributed to their more favorable initial condition compared to patients treated with VA ECMO. The disadvantages of VV ECMO include a longer operative time to place the cannulas, groin wound problems, and persistent leg swelling along with the necessity to convert some patients to VA ECMO. Although this experience demonstrates that newborns with severe respiratory failure can be supported with VV ECMO, the complications and lack of practical advantages over VA lead us to recommend VA ECMO for routine clinical use at present.

Female↗
PubMed1984

Ventricular arrhythmias during exercise testing: mechanism, response to coronary bypass surgery and prognostic significance.

To investigate the determinants and prognostic significance of ventricular arrhythmias during exercise testing, 86 patients with such arrhythmias were identified from a consecutive series of 446 patients who underwent treadmill exercise testing and cardiac catheterization. The prevalence of these arrhythmias was 19% in the total group but increased to 30% in the 120 patients with 3-vessel or left main coronary artery disease. Patients with exercise-induced arrhythmias were more likely to have 3-vessel or left main coronary artery disease, a lower resting ejection fraction, greater than or equal to 2 mm of ischemic ST depression and more severe segmental wall motion abnormalities than patients without this finding (p less than 0.05). Repeat exercise testing in 22 patients with exercise-induced arrhythmias after coronary bypass surgery revealed that persistence of these arrhythmias was associated with either severe wall motion abnormalities preoperatively or residual ischemic ST depression during the post-operative exercise testing. At a mean follow-up period of 5.3 years, the presence of exercise-induced ventricular arrhythmias was not associated with increased cardiac mortality in the medically treated patients.

Arrhythmias, Cardiac↗
PubMed1984

The efficacy and safety of high-dose verapamil and diltiazem in the long-term treatment of stable exertional angina.

The efficacy and safety of high-dose verapamil (480 mg/day) and diltiazem therapy (360 mg/day) were compared in separate cohorts of 26 and 20 patients, respectively. All patients had stable exertional angina and underwent an initial 6-week double-blind, placebo-controlled, randomized phase followed by a 12-month open-label period. Angina attacks were reduced by verapamil (6.3 +/- 7.5 to 2.5 +/- 4.1 attacks per week, p less than 0.001) and by diltiazem (9.2 +/- 7.5 to 3.0 +/- 3.1 attacks per week, p less than 0.001), while treadmill time increased with both verapamil (372 +/- 132 to 444 +/- 108 s, p less than 0.001) and diltiazem (412 +/- 175 to 536 +/- 164 s, p less than 0.001) during the short-term study. Both agents continued to show similar salutory effects at the end of one year. The beneficial effects of both drugs appeared to be related in part to a reduction of the rate-pressure product during submaximal exercise (12% by verapamil, 7% by diltiazem, both p less than 0.05). Adverse effects were few and consisted primarily of mild constipation in six patients taking verapamil, and pedal edema and transient flushing in 2 patients each using diltiazem. Thus, high-dose verapamil and diltiazem have similar beneficial effects and are safe for the long-term treatment of effort-related angina pectoris.

Angina Pectoris↗
PubMed1984

New break-away needle for subclavian vein cannulation.

A new break-away needle for subclavian catheter insertion has been described. This needle functions exactly as the usual 14 gauge needle, but it can be completely removed from the catheter while leaving the integral Luer adaptor intact.

Catheterization↗
PubMed1984

Clinical evaluation of a new rapid heparin assay using the dye azure A.

At the present time, heparin assays are based on biologic measures of activity. They are time-consuming, difficult to reproduce, and require special devices. We have developed a colorimetric assay for chemical heparin in plasma based on the metachromasia of azure A in the presence of heparin. One milliliter of plasma is added to 1 ml of 0.08 percent azure A, vortex mixed, and read at 620 nm in a spectrophotometer. To evaluate the clinical utility of this assay, we compared it to two biologic assays of heparin effect, activated PTT and activated clotting time, and to heparin levels determined by protamine titration in 113 samples from 28 patients undergoing cardiopulmonary bypass. The activated PTT in 94 of 113 samples was greater than 600 seconds, making this test not useful due to the time required and the lack of an end point. The activated clotting time of 80 samples was less than 600 seconds. The azure A measurement of heparin concentration correlated well in this group (correlation coefficient of 0.88, p less than or equal to 0.0001). Protamine titration determinations also had excellent correlation with azure A measurements in the 111 samples tested (correlation coefficient of 0.85, p less than or equal to 0.0001). The azure A assay correlates well with the standard measures of both heparin activity and heparin concentration. It is more rapid, simple, and less expensive than either of these, and it does not depend on a bioassay of coagulation as an end point. Chemical heparin measurements with azure A may be more useful clinically than the biologic assays in determining the reversal dose of protamine.

Adult↗
PubMed1984

Hirschsprung's disease in the newborn.

Hirschsprung's disease has become a more common cause of newborn intestinal obstruction in the past 30 years. In a group of 137 newborns with intestinal obstruction the most common diagnosis was necrotizing enterocolitis. The second most common cause, however, was Hirschsprung's disease. We have reviewed 26 infants with aganglionosis who presented at 32 days of age or less between 1972 and 1978. The average age at presentation was 8.3 days. There were 21 males and five females. Five infants had long-segment or total colonic disease. There was only one premature infant (34 weeks, 1840 g). The mean birthweight in the series was 3.6 kg. Six children had a family history of a congenital anomaly (23%). Three of these had a family history of Hirschsprung's disease (12%). Nine infants (35%) had associated congenital anomalies. Four of these newborns had Down's syndrome, and all four had a cardiac anomaly as well. Fifteen newborns presented with emesis (58%) which was bilious in nine (35%) cases. Seventeen babies (65%) had abdominal distension at the time of presentation. Eleven infants passed a meconium stool by 24 hours of age (42%), and 15 had passed meconium by 48 hours (58%). Twenty-two of 24 (92%) barium enema examinations available prior to diagnosis were diagnostic of Hirschsprung's disease. All of the 23 suction rectal biopsies were positive. All 26 patients underwent a colostomy or ileostomy following diagnosis. There was no enterocolitis and no mortality. All 26 patients have had an endorectal pullthrough performed at a mean age of 11.8 months without major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1984

Plasma verapamil levels and exercise performance.

Our study in 10 patients with stable, exercise-related angina under a double-blind, placebo-controlled protocol correlated plasma verapamil levels after single oral doses of 120 and 240 mg and exercise performance. Plasma verapamil levels peaked at 2 hr in seven patients and 4 hr in three patients and declined thereafter, with a mean plasma t1/2 of 3.22 and 4.54 hr after the 120- and 240-mg dose. Despite the relatively short t1/2s, total exercise duration and time to onset of angina and S-T segment depression were longer than placebo values for 4 hr after the 120-mg dose and for 8 hr after the 240-mg dose. Percentage increase in treadmill time and log of plasma verapamil levels correlated. All patients with plasma levels above 100 ng/ml had at least a 50% increase in exercise duration. Thus measurement of plasma verapamil levels are useful in patients who fail to respond to a dose of verapamil. If the level is below 100 ng/ml, increasing the dose of verapamil may improve response.

Administration, Oral↗